Non-invasive analysis is a valuable technique for acquiring information about systems or targets without undesirable side effects, such as damaging the target or system being analyzed. In the case of analyzing living entities, such as human tissue, undesirable side effects of invasive analysis include the risk of infection along with pain and discomfort associated with the invasive process.
In the particular case of measurement of blood glucose levels in diabetic patients, it is highly desirable to measure the blood glucose level frequently and accurately to provide appropriate treatment of the diabetic condition as absence of appropriate treatment can lead to potentially fatal health issues, including kidney failure, heart disease or stroke. A non-invasive method would avoid the pain and risk of infection and provide an opportunity for frequent or continuous measurement.
Non-invasive glucose analysis based on several techniques have been proposed. These techniques include: near infrared spectroscopy using both transmission and reflectance; spatially resolved diffuse reflectance; frequency domain reflectance; fluorescence spectroscopy; polarimetry and Raman spectroscopy.
These techniques are vulnerable to inaccuracies due to issues such as, environmental changes, presence of varying amounts of interfering contamination and skin heterogeneity. These techniques also require considerable processing to de-convolute the required measurement, typically using multi-variate analysis. These techniques have heretofore produced insufficient accuracy and reliability to be clinically useful.
More recently optical coherence tomography (OCT), using a super-luminescent diode (SLD) as the optical source, has been proposed in Proceedings of SPIE, Vol. 4263, pages 83-90 (2001). The SLD output beam has a broad bandwidth and short coherence length. The technique involves splitting the output beam into a probe and reference beam. The probe beam is applied to the system to be analyzed (the target). Light scattered back from the target is combined with the reference beam to form the measurement signal.
Because of the short coherence length only light that is scattered from a depth within the target such that the total optical path lengths of the probe and reference are equal combine interferometrically. Thus the interferometric signal provides a measurement of the scattering value at a particular depth within the target. By varying the length of the reference path length, a measurement of the scattering values at various depths can be measured and thus the scattering value as a function of depth can be measured.
The correlation between blood glucose concentration and the scattering coefficient of tissue has been reported in Optics Letters, Vol. 19, No. 24, Dec. 15, 1994 pages 2062-2064. The change of the scattering coefficient correlates with the glucose concentration and therefore measuring the change of the scattering value with depth provides a measurement of the scattering coefficient which provides a measurement of the glucose concentration. Determining the glucose concentration from a change, rather than an absolute value provides insensitivity to environmental conditions.
In conventional OCT systems depth scanning is achieved by modifying the relative optical path length of the reference path and the probe path. The relative path length is modified by such techniques as electromechanical based technologies, such as galvanometers or moving coils actuators, rapid scanning optical delay lines and rotating polygons. All of these techniques involve moving parts, which have limited scan speeds and present significant alignment and associated signal to noise ratio related problems.
Motion occurring within the duration of a scan can cause significant problems in correct signal detection. If motion occurs within a scan duration, motion related artifacts will be indistinguishable from real signal information in the detected signal, leading to an inaccurate measurement. Long physical scans, for larger signal differentiation or locating reference areas, increase the severity of motion artifacts. Problematic motion can also include variation of the orientation of the target surface (skin) where small variations can have significant effects on measured scattering intensities.
Non-moving part solutions, include acousto-optic scanning, can be high speed, however such solutions are costly, bulky and have significant thermal control and associated thermal signal to noise ratio related problems.
Optical fiber based OCT systems also use piezo electric fiber stretchers. These, however, have polarization rotation related signal to noise ratio problems and also are physically bulky, are expensive, require relatively high voltage control systems and also have the motion related issues. These aspects cause conventional OCT systems to have significant undesirable signal to noise characteristics and present problems in practical implementations with sufficient accuracy, compactness and robustness for commercially viable and clinically accurate devices.
Therefore there is an unmet need for commercially viable, compact, robust, non-invasive device with sufficient accuracy, precision and repeatability to image or analyze targets or to measure analyte concentrations, and in particular to measure glucose concentration in human tissue.